Martin Scheer

Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.

We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 × 10−24. The odds ratio was 2.57 (95% CI = 2.02–3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88–9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.

Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate

We conducted a genome-wide association study for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in 401 affected individuals and 1,323 controls, with replication in an independent sample of 793 NSCL/P triads. We report two new loci associated with NSCL/P at 17q22 (rs227731, combined P = 1.07 × 10−8, relative risk in homozygotes = 1.84, 95% CI 1.34–2.53) and 10q25.3 (rs7078160, combined P = 1.92 × 10−8, relative risk in homozygotes = 2.17, 95% CI 1.32–3.56).

Recurrent chromosomal imbalances detected in biopsy material from oral premalignant and malignant lesions by combined tissue microdissection, universal DNA amplification, and comparative genomic hybridization

Biopsies routinely performed for the histopathological diagnosis of oral epithelial lesions before treatment were screened for chromosomal imbalances by comparative genomic hybridization. Comparative genomic hybridization was performed on 12 oral premalignant lesions (OPLs; dysplasias and carcinomas in situ) and 14 oral squamous cell carcinomas (OSCCs). Eight biopsies displayed areas of different histopathological appearance, so that OPLs and OSCCs from the same patient were analyzed. To avoid contamination with nonneoplastic cells, defined cell populations were isolated by micromanipulation with a glass needle. Before comparative genomic hybridization analysis, universal DNA amplification was performed using the DOP-polymerase chain reaction protocol. In the 14 OSCCs examined, the average number of chromosomal imbalances was significantly higher than in the 12 OPLs (mean +/- SEM: 11.9 +/- 1.9 versus 3.2 +/- 1.2; P = 0.003). The DNA copy number changes identified in more than one OPL were gains on 8q (3 of 12) and 16p (2 of 12), as well as losses on 3p (5 of 12); 5q (4 of 12); 13q (3 of 12); and 4q, 8p, and 9p (2 of 12 each). In more than 30% of OSCCs, gains of chromosomal material were identified on 20q (8 of 14); 8q, 11q, 22q (7 of 14 each); 3q, 15q, and 17p (6 of 14 each); and 14q, 17q, and 20p (5 of 14 each), and losses were identified on 3p and 4q (9 of 14 each), 5q (7 of 14), 13q (6 of 14), and 2q and 9p (5 of 14 each). These results were validated by positive and negative control comparative genomic hybridization experiments and microsatellite analysis for the detection of allelic loss. The vast majority of genomic alterations found in OPLs were again identified in OSCCs from the same biopsy, supporting the hypothesis that multiple lesions in the same patient are clonally related. In summary, we show that comprehensive information on the genomic alterations in oral epithelial lesions can be obtained from small biopsies. Such data may identify prognostic indicators that could eventually assist in designing therapeutic strategies.

Impact of podoplanin expression in oral squamous cell carcinoma: clinical and histopathologic correlations

Cervical lymph node metastases reduce the overall survival of patients with oral squamous cell carcinoma (OSCC) and require a neck dissection. However, elective management of a clinical N0 neck remains a controversial topic, as there are no reliable factors available predicting cervical lymph node metastases. Recent studies suggest an impact of podoplanin expression on metastatic spread to the cervical lymph nodes. Our aim was to investigate the influence of podoplanin expression on prognosis and metastatic lymphatic spread. In our retrospective study, podoplanin expression was examined in a set of 80 patients with OSCC by immunhistochemistry. We analysed associations between the level of podoplanin expression and various clinicopathologic parameters. In 67 patients (84%), podoplanin was expressed on the tumour cells. Nineteen patients (24%) showed high levels of expression. The 5-year overall survival (31%) for patients with high levels of podoplanin expression was significantly lower (p < 0.001) than for patients with low and moderate expression of podoplanin (93% and 65%, respectively). There was an association between podoplanin expression and the frequency of cervical lymph node metastases. Cervical lymph node metastases were found in 79% of the patients with high podoplanin expression, while patients with weak podoplanin expression had metastases in only 22% (p < 0.001). None of the 13 patients without podoplanin expression had cervical lymph node metastases. We concluded that podoplanin is expressed frequently in OSCC and that podoplanin expression correlates with cervical lymph node metastases and clinical outcome.

Growth and Proliferation of Human Osteoblasts on Different Bone Graft Substitutes An In Vitro Study

The purpose of this study was to investigate the effect of different bone graft substitutes onto the growth and proliferation pattern of bone cells derived from human iliac cancellous bone. Five different bone graft materials were used to investigate the effect on the proliferation of osteoblasts in vitro: phytogene hydroxyapatite (Algipore®), &agr;-Tricalcium phosphate (Bio-Base®), bovine hydroxyapatite (low temperature) (Bio-Oss®), bovine hydroxyapatite (high temperature) (Osteograf®), and bovine hydroxyapatite (high temperature) enhanced with p-15, synthetic peptide (PepGen p-15®). The osteoblasts were derived from human iliac cancellous bone and seeded with the different bone substitutes. The cell proliferation and viability (WST-1), alkaline phosphatase as an early marker of osteoblast proliferation, was evaluated after 6 and 9 days. The cultures were examined for cell growth pattern and morphology by normal light and scanning electron microscopy. The human osteoblasts showed a different proliferation pattern according to the type of applied bone graft substitute. PepGen P-15 showed the highest proliferation and differentiation rate followed by Osteograf, Algipore, and Bio-base. Bio-Oss showed the lowest. These results were confirmed by electron microscopy and light microscopy evaluation in which similar growth pattern were observed. Distinct bone graft materials have different impact onto the proliferation pattern of human osteoblasts in vitro.

Comparison of cone-beam volumetric imaging and combined plain radiographs for localization of the mandibular canal before removal of impacted lower third molars

OBJECTIVE The removal of third molars requires information about the relative position of the root tips and the mandibular nerve. The diagnostic value of conventional radiologic procedures using a panoramic radiograph and symmetrical PA cephalometric radiograph (PAN&PA) was compared with that of a cone-beam volumetric imaging (CBVI) device (Galileos; Sirona, Bensheim, Germany). STUDY DESIGN Six observers evaluated 30 PAN&PA and 30 CBVI for the position of root tips. Diagnostic information was rated from 1 to 5 (excellent to poor). RESULTS With PAN&PA, 3 times more scans showed nondetectable information for horizontal position compared with CBVI. The diagnostic information in the vertical dimension received a median rating of 2 (good) for CBVI and for PAN & PA; for the horizontal dimension, CBVI received a median rating of 2 (good), compared with a significantly worse median rating of 3 (sufficient) for PAN & PA (P = .000). The variance was highest for the horizontal dimension with PAN & PA (1.27). CONCLUSION These findings indicate that cone-beam technology improves the localization of third molar for presurgical planning.

Prevalence of pathologic findings in the maxillary sinus in cone-beam computerized tomography

OBJECTIVE The aim of this study was to assess the prevalence of pathologic findings in the maxillary sinus by using cone-beam computerized tomography (CBCT). STUDY DESIGN One thousand twenty-nine consecutive CBCT scans were retrospectively inspected for pathologic findings in the maxillary sinus by 3 observers. Findings were differentiated by mucosal thickening, partial opacification with liquid accumulation, total opacification, and polypoidal mucosal thickening. Position and diameter of the maxillary sinus ostium were assessed. Correlations for pathologic findings and the factors of age and gender were calculated. Patients with clinical manifestations of sinusitis or total opacification in either sinus were reevaluated. RESULTS A total prevalence for pathologies in the maxillary sinus of 56.3% was found in this study. The most frequent pathology was mucosal thickening. Patients >60 years of age showed significantly more pathologies in the maxillary sinus (P = .02), and male patients showed significantly more pathologies than female patients (P = .01). Clinical signs of sinusitis could be confirmed on CBCT images for all patients. CONCLUSIONS Pathologies in the maxillary sinus are frequently found in CBCT imaging and have to be treated or followed-up accordingly. CBCT is applicable for diagnosis and treatment planning of clinically present sinusitis.

Autofluorescence imaging of potentially malignant mucosa lesions

OBJECTIVE AND STUDY DESIGN Several noninvasive adjunctive methods have been proposed for identification of potentially malignant mucosa lesions. The VELscope is an optical device for detecting spatial changes in mucosa autofluorescence caused by premalignant lesions in conjunction with an intraoral exam. The aim of our prospective study was to correlate loss of autofluorescence from undiagnosed mucosa lesions with histology. RESULTS In total 64 patients considered at risk for squamous cell carcinoma (20 had previous OSCC) were included in the study. Regions with fluorescence visualization loss were considered as malignant or dysplastic. All patients underwent biopsy after VELscope examination. In 22 patients (34.4%) a loss of autofluorescence indicating a squamous intraepithelial neoplasia (SIN) or malignant mucosal lesion was detected. The sensitivity of identification of malignant and dysplastic areas with the VELscope was 100% and the specificity was 80.8%, respectively, compared with histology as gold standard. The positive predictive value was 54.5% and the negative predictive value was 100% respectively. CONCLUSION Evaluation of autofluorescence imaging with VELscope can assist in the identification of malignant and potentially malignant oral lesions from normal mucosa in high-risk patients but does not help discriminating benign lesions from malignant or premalignant mucosal conditions.

Concise Review: Induced Pluripotent Stem Cells and Lineage Reprogramming: Prospects for Bone Regeneration†‡§

Bone tissue for transplantation therapies is in high demand in clinics. Osteodegenerative diseases, in particular, osteoporosis and osteoarthritis, represent serious public health issues affecting a respectable proportion of the elderly population. Furthermore, congenital indispositions from the spectrum of craniofacial malformations such as cleft palates and systemic disorders including osteogenesis imperfecta are further increasing the need for bone tissue. Additionally, the reconstruction of fractured bone elements after accidents and the consumption of bone parts during surgical tumor excisions represent frequent clinical situations with deficient availability of healthy bone tissue for therapeutic transplantations. Epigenetic reprogramming represents a powerful technology for the generation of healthy patient‐specific cells to replace or repair diseased or damaged tissue. The recent generation of induced pluripotent stem cells (iPSCs) is probably the most promising among these approaches dominating the literature of current stem cell research. It allows the generation of pluripotent stem cells from adult human skin cells from which potentially all cell types of the human body could be obtained. Another technique to produce clinically interesting cell types is direct lineage reprogramming (LR) with the additional advantage that it can be applied directly in vivo to reconstitute a damaged organ. Here, we want to present the two technologies of iPSCs and LR, to outline the current states of research, and to discuss possible strategies for their implementation in bone regeneration. STEM CELLS 2011;29:555–563

Prognostic value of the sixth edition of the UICC's TNM classification and stage grouping for oral cancer.

Carcinoma of the oral cavity is classified according to the TNM staging system of the UICC. The staging system is under continuous revision. The aim of our study was to assess the prognostic value of the UICC sixth edition for oral cancer, which was established in 2003.